Phylogenetic analyses of 159 DNA sequences from the nuclear rDNA internal transcribed spacer region were conducted to evaluate the monophyly of the herbaceous, perennial genera of Apiaceae subfamily Apioideae endemic to North America (north of Mexico) and to determine the relationships of those elements that currently comprise Cymopterus within the group. The results of a previous phylogenetic study were equivocal in suggesting monophyly for these perennial, endemic taxa and revealed Cymopterus to be polyphyletic, with its species closely linked with those of Aletes, Lomatium, Musineon, Oreoxis, Orogenia, Podistera, Pseudocymopterus, Pteryxia, and Tauschia. Herein, we expand sampling to include comprehensive representation of Aletes, Cymopterus, Musineon, Oreoxis, Orogenia, Podistera, Pseudocymopterus, and Pteryxia, and greater representation of Lomatium and Tauschia. We also include all members of two genera not examined previously, Glehnia and Oreonana, as well as additional outgroup genera from the Angelica clade of the apioid superclade. Our results indicate that the perennial, endemic apioid umbellifers of North America constitute a (weakly supported) monophyletic group, with Angelica and the meso-American Arracacia clade comprising two of several possible sister groups. The two subspecies of Glehnia littoralis ally with Angelica and Peucedanum japonicum; Oreonana shows affinity with several species of Cymopterus and Lomatium. The lack of resolution in the ITS trees precludes unambiguous hypotheses of relationship among these perennial, endemic umbellifers but does show that many of these genera, where resolved, are not monophyletic. Indeed, Cymopterus and Lomatium are highly polyphyletic and permeate all major clades resolved in the molecule-derived trees. Evidence from branch lengths and low sequence divergence suggests that this group of North American umbellifers underwent rapid radiation, likely during the geoclimatic events of the Late Tertiary and Quaternary.